72 research outputs found
Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals
Nerve terminal invasion by an axonal spike activates voltage-gated channels, triggering calcium entry, vesicle fusion, and release of neurotransmitter. Ion channels activated at the terminal shape the presynaptic spike and so regulate the magnitude and duration of calcium entry. Consequently characterization of the functional properties of ion channels at nerve terminals is crucial to understand the regulation of transmitter release. Direct recordings from small neocortical nerve terminals have revealed that external [Ca(2+)] ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify the first component in a presynaptic calcium signaling pathway.By combining genetic and pharmacological approaches with direct patch-clamp recordings from small acutely isolated neocortical nerve terminals we identify the extracellular calcium sensor. Our results show that the calcium-sensing receptor (CaSR), a previously identified G-protein coupled receptor that is the mainstay in serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist, reduced NSCC currents in direct terminal recordings in a dose-dependent and reversible manner. In contrast, glutamate and GABA did not affect the NSCC currents.Our experiments identify CaSR as the first component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in [Ca(2+)](o) and increase action potential duration by increasing NSCC activity, thereby attenuating the impact of decreases in [Ca(2+)](o) on release probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and provide presynaptic feedback that will alter brain excitability
Synthesis of Saturated Heterocycles via Metal-Catalyzed Formal Cycloaddition Reactions That Generate a C–N or C–O Bond
Highly conserved regulation of cohesin-mediated chromosome folding between yeast and mammals
Raw microscopy images used in the stud
Regulation of cohesin-mediated mitotic chromosome folding by Eco1 and other partners
Raw microscopy images used in the stud
Highly conserved regulation of cohesin-mediated chromosome folding between yeast and mammals
Raw microscopy images used in the stud
Enantiospecific Total Synthesis of (-)-Polyoxamic Acid Using 2, 3-Aziridino-gamma-lactone Methodology.
Intramolecular C-N Bond Formation Reactions Catalyzed by Ruthenium Porphyrins: Amidation of Sulfamate Esters and Aziridination of Unsaturated Sulfonamides
Rhodium(II,II) Dimer as an Efficient Catalyst for Aziridination of Sulfonamides and Amidation of Steroids
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